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61.
Tai‐An Chiang Yu‐Lin Yang Ya‐Ying Yang Min‐Hsiu Hu Pei‐Fen Wu Shu‐Fen Liu Ruay‐Ming Huang Tung‐Nan Liao Chien‐Ya Hung Tsung‐Jen Hung Tao‐Chen Lee 《Journal of cellular biochemistry》2010,109(4):663-671
Hyperosmolarity plays an essential role in the pathogenesis of diabetic tubular fibrosis. However, the mechanism of the involvement of hyperosmolarity remains unclear. In this study, mannitol was used to evaluate the effects of hyperosmolarity on a renal distal tubule cell line (MDCK). We investigated transforming growth factor‐β receptors and their downstream fibrogenic signal proteins. We show that hyperosmolarity significantly enhances the susceptibility to exogenous transforming growth factor (TGF)‐β1, as mannitol (27.5 mM) significantly enhanced the TGF‐β1‐induced increase in fibronectin levels compared with control experiments (5.5 mM). Specifically, hyperosmolarity induced tyrosine phosphorylation on TGF‐β RII at 336 residues in a time (0–24 h) and dose (5.5–38.5 mM) dependent manner. In addition, hyperosmolarity increased the level of TGF‐β RI in a dose‐ and time‐course dependent manner. These observations may be closely related to decreased catabolism of TGF‐β RI. Hyperosmolarity significantly downregulated the expression of an inhibitory Smad (Smad7), decreased the level of Smurf 1, and reduced ubiquitination of TGF‐β RI. In addition, through the use of cycloheximide and the proteasome inhibitor MG132, we showed that hyperosmolarity significantly increased the half‐life and inhibited the protein level of TGF‐β RI by polyubiquitination and proteasomal degradation. Taken together, our data suggest that hyperosmolarity enhances cellular susceptibility to renal tubular fibrosis by activating the Smad7 pathway and increasing the stability of type I TGF‐β receptors by retarding proteasomal degradation of TGF‐β RI. This study clarifies the mechanism underlying hyperosmotic‐induced renal fibrosis in renal distal tubule cells. J. Cell. Biochem. 109: 663–671, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
62.
Fang Liu Kratika Singhal Rowan Matney Swati Acharya Cezmi A. Akdis Kari C. Nadeau Allis S. Chien Ryan D. Leib 《Proteomics》2020,20(11)
The analytical scale of most mass‐spectrometry‐based targeted proteomics assays is usually limited by assay performance and instrument utilization. A recently introduced method, called triggered by offset, multiplexed, accurate mass, high resolution, and absolute quantitation (TOMAHAQ), combines both peptide and sample multiplexing to simultaneously improve analytical scale and quantitative performance. In the present work, critical technical requirements and data analysis considerations for successful implementation of the TOMAHAQ technique based on the study of a total of 185 target peptides across over 200 clinical plasma samples are discussed. Importantly, it is observed that significant interference originate from the TMTzero reporter ion used for the synthetic trigger peptides. This interference is not expected because only TMT10plex reporter ions from the target peptides should be observed under typical TOMAHAQ conditions. In order to unlock the great promise of the technique for high throughput quantification, here a post‐acquisition data correction strategy to deconvolute the reporter ion superposition and recover reliable data is proposed. 相似文献
63.
Alex Zaufel Sandra M.W. van de Wiel Lu Yin Günter Fauler Daphne Chien Xinzhong Dong John F. Gilmer Jennifer K. Truong Paul A. Dawson Stan F.J. van de Graaf Peter Fickert Tarek Moustafa 《生物化学与生物物理学报:疾病的分子基础》2021,1867(8):166153
IsoBAs, stereoisomers of primary and secondary BAs, are found in feces and plasma of human individuals. BA signaling via the nuclear receptor FXR is crucial for regulation of hepatic and intestinal physiology/pathophysiology. Aim: Investigate the ability of BA-stereoisomers to bind and modulate FXR under physiological/pathological conditions. Methods: Expression-profiling, luciferase-assays, fluorescence-based coactivator-association assays, administration of (iso)-BAs to WT and cholestatic mice. Results: Compared to CDCA/isoCDCA, administration of DCA/isoDCA, UDCA/isoUDCA only slightly increased mRNA expression of FXR target genes; the induction was more evident looking at pre-mRNAs. Notably, almost 50% of isoBAs were metabolized to 3-oxo-BAs within 4 h in cell-based assays, making it difficult to study their actions. FRET-based real-time monitoring of FXR activity revealed that isoCDCA>CDCA stimulated FXR, and isoDCA and isoUDCA allowed fully activated FXR to be re-stimulated by a second dose of GW4064. In vivo co-administration of a single dose of isoBAs followed by GW4064 cooperatively activated FXR, as did feeding of UDCA in a background of endogenous FXR ligands. However, in animals with biliary obstruction and concomitant loss of intestinal BAs, UDCA was unable to increase intestinal Fgf15. In contrast, mice with an impaired enterohepatic circulation of BAs (Asbt?/?, Ostα?/?), administration of UDCA was still able to induce ileal Fgf15 and repress hepatic BA-synthesis, arguing that UDCA is only effective in the presence of endogenous FXR ligands. Conclusion: Secondary (iso)BAs cooperatively activate FXR in the presence of endogenous BAs, which is important to consider in diseases linked to disturbances in BA enterohepatic cycling. 相似文献
64.
65.
Interleukin-17 (IL-17), a pro-inflammatory cytokine produced by CD4+ Th17 cells, has been associated with the pathogenesis of several autoimmune diseases including uveitis. The fate of IL-17 during HIV/AIDS, however, remains unclear, and a possible role for IL-17 in the pathogenesis of AIDS-related diseases has not been investigated. Toward these ends, we performed studies using a well-established animal model of experimental murine cytomegalovirus (MCMV) retinitis that develops in C57/BL6 mice with retrovirus-induced immunosuppression (MAIDS). After establishing baseline levels for IL-17 production in whole splenic cells of healthy mice, we observed a significant increase in IL-17 mRNA levels in whole splenic cells of mice with MAIDS of 4-weeks (MAIDS-4), 8-weeks (MAIDS-8), and 10-weeks (MAIDS-10) duration. In contrast, enriched populations of splenic CD4+ T cells, splenic macrophages, and splenic neutrophils exhibited a reproducible decrease in levels of IL-17 mRNA during MAIDS progression. To explore a possible role for IL-17 during the pathogenesis of MAIDS-related MCMV retinitis, we first demonstrated constitutive IL-17 expression in retinal photoreceptor cells of uninfected eyes of healthy mice. Subsequent studies, however, revealed a significant decrease in intraocular levels of IL-17 mRNA and protein in MCMV-infected eyes of MAIDS-10 mice during retinitis development. That MCMV infection might cause a remarkable downregulation of IL-17 production was supported further by the finding that systemic MCMV infection of healthy, MAIDS-4, or MAIDS-10 mice also significantly decreased IL-17 mRNA production by splenic CD4+ T cells. Based on additional studies using IL-10 ?/? mice infected systemically with MCMV and IL-10 ?/? mice with MAIDS infected intraocularly with MCMV, we propose that MCMV infection downregulates IL-17 production via stimulation of suppressor of cytokine signaling (SOCS)-3 and interleukin-10. 相似文献
66.
Sponsored by Waters Corporation organized by the Education Committee: Dr. Kevin L. Knudtson Dr. Allis S. Chien Dr Natalia G. Reyero Vinas Dr LeRoy Martin Dr. Janet M Murray Dr. Paul A Rudnick Brian C. Searle Michael Zianni Tim C Hunter James Van Ee David Needleman Elke Kuster-Schock 《Journal of biomolecular techniques》2013,24(2):112
67.
Since the uncertainty involved in demand forecast is increasingly amplified with the forecast lead-time, high-tech companies often suffer the risks of oversupply and shortage of capacity that will affect the profitability and growth. High-tech industries including semiconductor and TFT-LCD industries are capital-intensive, in which the capacity plan and corresponding capital investment decisions are critical due to demand fluctuation. Once the capacity is planned, the company may suffer the risks of either low capital-effectiveness due to low capacity utilization and capacity oversupply, or poor customer satisfaction caused by the capacity shortage. Most of the existing studies focused on solving the long-term capacity shortage issue through optimizing the capacity investment plan, or medium-term capacity plan to allocate demands among the wafer fabrication facilities (fabs) to balance the loading and product mix. Focusing on a real setting, this study proposed a systematic decision method to analyze short-term solutions of cross-company capacity backup between the companies in the semiconductor industry ecosystem. In particular, a game theory and decision tree analysis model was developed to support this decision. A case study was conducted with real data of semiconductor manufacturing companies in Taiwan for validation. The results have demonstrated practical viability of this approach. The approach suggested has been implemented in this company. 相似文献
68.
Wei-Chien Huang Yi-Ling Hsieh Chao-Ming Hung Pei-Hsuan Chien Yu-Fong Chien Lei-Chin Chen Chih-Yen Tu Chia-Hung Chen Sheng-Chieh Hsu Yueh-Ming Lin Yun-Ju Chen 《PloS one》2013,8(12)
The multikinase inhibitor, sorafenib (Nexavar®, BAY43-9006), which inhibits both the Raf/MEK/ERK pathway and several receptor tyrosine kinases (RTKs), has shown significantly therapeutic benefits in advanced hepatocellular carcinoma (HCC). However, not all HCC patients respond to sorafenib well and new therapeutic strategies to optimize the efficacy of sorafenib are urgently required. Overexpression of breast cancer resistance protein (BCRP/ABCG2) mediates the drug-efflux of several tyrosine kinase inhibitors (TKIs) to attenuate their efficacy. This study aimed to investigate the role of BCRP/ABCG2 in the sensitivity of HCC to sorafenib. Our data showed that BCRP/ABCG2 mediated the efflux of sorafenib. Co-treatment with a BCRP/ABCG2 inhibitor greatly augmented the cytotoxicity of sorafenib in HCC cells. Similar results were also achieved by the competitive inhibitor of BCRP/ABCG2, gefitinib, in combination with sorafenib. These results suggest not only that BCRP/ABCG2 is a potential predictor for the sorafenib sensitivity in HCC, but also that blockage of BCRP/ABCG2 may be a potential strategy to increase the response of HCC cells to sorafenib. 相似文献
69.
Chia-Ching Liaw Yu-Chen Chen Ahmed Eid Fazary Ju-Liang Hsieh Shun-Ying Chen Ching-Te Chien Shiow-Yunn Sheu Yao-Haur Kuo Bor-Luen Chiang Ya-Ching Shen 《Phytochemistry letters》2013,6(3):397-402
A novel C6–C3 prenylated compound, illicarborene A (1), together with illioliganfunone D (2), 1-allyl-3,5-dimethoxy-4-(3-methylbut-2-enyloxy)benzene (3), (?)-illicinone A (4), (?)-illicinone B (5) and (?)-illicinone A derivative (6) was isolated and characterized from the fruits of Illicium arborescens Hayata. Compound 1 possesses a new class of tricyclic 6/6/5 ring system. The structure of 1 was determined by spectroscopic analysis such as 1H–1H COSY, HMQC, HMBC, and NOESY, and confirmed by chemical reaction to yield 7. Compounds 1–5 were found to increase proliferative activity in primary cell culture of osteoblast cells. 相似文献
70.
Hsin-Chou Yang Chih-Min Liu Yu-Li Liu Chia-Wei Chen Chien Ching Chang Cathy S. J. Fann Jen-Jie Chiou Ueng-Cheng Yang Chun-Houh Chen Stephen V. Faraone Ming T. Tsuang Hai-Gwo Hwu 《PloS one》2013,8(3)